Abstract
Although numerous marine bacteria are known to produce antibiotics via hybrid NRPS-PKS gene clusters, none have been previously described in an Alteromonas species. In this study, we describe in detail a novel hybrid NRPS-PKS cluster identified in the plasmid of the Alteromonas macleodii strain AltDE1 and analyze its relatedness to other similar gene clusters in a sequence-based characterization. This is a mobile cluster, flanked by transposase-like genes, that has even been found inserted into the chromosome of some Alteromonas macleodii strains. The cluster contains separate genes for NRPS and PKS activity. The sole PKS gene appears to carry a novel acyltransferase domain, quite divergent from those currently characterized. The predicted specificities of the adenylation domains of the NRPS genes suggest that the final compound has a backbone very similar to bleomycin related compounds. However, the lack of genes involved in sugar biosynthesis indicates that the final product is not a glycopeptide. Even in the absence of these genes, the presence of the cluster appears to confer complete or partial resistance to phleomycin, which may be attributed to a bleomycin-resistance-like protein identified within the cluster. This also suggests that the compound still shares significant structural similarity to bleomycin. Moreover, transcriptomic evidence indicates that the NRPS-PKS cluster is expressed. Such sequence-based approaches will be crucial to fully explore and analyze the diversity and potential of secondary metabolite production, especially from increasingly important sources like marine microbes.
Highlights
Marine bacteria are gaining prominence as producers of secondary metabolites, which display unique structural and functional characteristics [1,2]
A. macleodii strains isolated from the Mediterranean [27], contain this same cluster in either a plasmid, like AltDE1, or inserted in the chromosome, suggesting that it is a mobile cluster [22]. We describe this novel hybrid nonribosomal peptide synthetases (NRPS)-Polyketide synthases (PKS) in A. macleodii strain AltDE1 and provide evidence that suggests strong parallels between the hybrid NRPS-PKS cluster of A. macleodii and gene clusters involved in biosynthesis of bleomycin family of antitumor antibiotics produced by actinomycetes [28]
We describe in detail a novel, mobile, hybrid NRPS-PKS cluster first identified in the plasmid of the Alteromonas macleodii strain AltDE1 and provide evidence that this cluster is related to that of the bleomycin glycopeptide antibiotic family
Summary
Marine bacteria are gaining prominence as producers of secondary metabolites, which display unique structural and functional characteristics [1,2]. This emerging source of natural products is of particular importance due to a decline in antibiotic drug discovery from their traditional source (i.e., soil microbes) over the past two decades [3]. The striking similarities between PKs and NRPSs, both structural and catalytic, allow for the formation of hybrid clusters that contain elements of each class [5] These hybrid NRPS-PKS clusters provide even greater variety for potential secondary metabolites produced by microorganisms [6]
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